Kidney Week

Abstract: SA-PO937

The Role of Suppression of Tumorigenicity-2 (ST2) in the Peritoneal Fibrosis and Peritoneal Dialysis (PD) Outcomes

Session Information

• Dialysis: Peritoneal Dialysis - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 703 Dialysis: Peritoneal Dialysis

Authors

• Kim, Yong Chul, SNUH, Seoul, Korea (the Republic of)

Yong Chul Kim,

• Yu, Mi-yeon, SNUH, Seoul, Korea (the Republic of)

Mi-yeon Yu,

• Lee, Hajeong, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Hajeong Lee,

• Oh, Yun Jung, Cheju Halla General Hospital, Jeju, Korea (the Republic of)

Yun Jung Oh,

• Lee, Jae Wook, National Cancer Center, Seoul, Korea (the Republic of)

Jae Wook Lee,

• Jeon, Un Sil, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates

Un Sil Jeon,

• Lee, Jung Pyo, Seoul National University Boramae Medical Center, Seoul, Korea (the Republic of)

Jung Pyo Lee,

• Oh, Kook-Hwan, Seoul National University Hospital, Seoul, Korea (the Republic of)

Kook-Hwan Oh,

• Cha, Ran-hui, National Medical Center, Seoul, Korea (the Republic of)

Ran-hui Cha,

• Yang, Seung Hee, Kidney Research Institute, Seoul National University, Seoul, Korea (the Republic of)

Seung Hee Yang,

• Kim, Yon Su, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Yon Su Kim,

Background

Peritoneal fibrosis (PF) is an intractable complication which leads to peritoneal membrane failure in PD. The aim of this study is to investigate the role of ST2 involved in PF.

Methods

Samples of dialysate and clinical data were prospectively collected from 54 patients at Seoul National University Hospital between 2010 and 2016. Dialysate soluble ST2 (sST2) levels were measured after 1 month of PD initiation (baseline) using the ELISA technique. Fibrosis induced by TGFβ and high concentration of glucose in primary cultured human peritoneal mesothelial cells (HPMCs) were evaluated with ST2, fibronectin, β-galactosidase, snail and E-cadherin protein expressions. Anti-ST2 monoclonal antibody (mAb) was treated to evaluate the neutralizing effect of ST2 on PF. Immunohistochemistry (IHC) stain of ST2 was performed in peritoneum tissue samples of chlorhexidine gluconate (CG)-induced PF mice and control.

Results

Baseline dialysate sST2 (sST2-b) levels were 2063.4 ± 2457.8 pg/mL and mean duration of follow-up periods was 53.4 ± 18.8 months. We observed that patients who changed dialysis modality to hemodialysis due to PD failure had high sST2-b levels in peritoneal effluent compared with others (1576.2 ± 199.9 vs 4143.1 ± 1107.3, P = 0.03). High sST2-b was associated with a hazard ratio (HR) for PD failure of 7.72 (95% CI 1.10-54.3, P = 0.04) in a fully adjusted model. sST2-b showed a good performance of predicting PD failure; the area under the ROC curve was 0.784 (P = 0.001). We found that in primary cultured HPMCs, TGFβ treatment increased protein expressions of ST2, fibronectin, β-galactosidase, snail and decreased expression of E-cadherin in a dose-dependent manner. Protein expression of ST2 and fibronectin were decreased after anti-ST2 Ab administration. High concentration of glucose (100mmol/L) also induced fibrosis in HPMCs and fibrosis was ameliorated after treating anti-ST2 Ab. ST2 was found in fibroblasts and mesothelial cells within the underlying submesothelial zones of CG-induced PF mice.

Conclusion

Elevated dialysate levels of sST2 is associated with PD failure. Thus, an elevated dialysate levels of ST2 appears to play a role in fibrosis and inflammation during peritoneal injury. And ST2 blockade is a potential therapeutic target for renal preservation.